The era of GWAS is over – Yes

Vandenbroeck, Koen

doi:10.1177/1352458517738059

Cited by 2 publications

(2 citation statements)

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“…To properly address the germline questions, it will be important to standardize platforms and methodological approaches. The implementation of bioinformatics pipelines, such as fine mapping strategies to prioritize putative functional variants and to identify true causal associations, will be critical [92, 93]. Direct genome-editing techniques, e.g.…”

Section: Germline Genetic Contributions To Cirmentioning

confidence: 99%

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Toward a comprehensive view of cancer immune responsiveness: a synopsis from the SITC workshop

Bedognetti¹,

Ceccarelli²,

Galluzzi³

et al. 2019

j. immunotherapy cancer

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Tumor immunology has changed the landscape of cancer treatment. Yet, not all patients benefit as cancer immune responsiveness (CIR) remains a limitation in a considerable proportion of cases. The multifactorial determinants of CIR include the genetic makeup of the patient, the genomic instability central to cancer development, the evolutionary emergence of cancer phenotypes under the influence of immune editing, and external modifiers such as demographics, environment, treatment potency, co-morbidities and cancer-independent alterations including immune homeostasis and polymorphisms in the major and minor histocompatibility molecules, cytokines, and chemokines. Based on the premise that cancer is fundamentally a disorder of the genes arising within a cell biologic process, whose deviations from normality determine the rules of engagement with the host’s response, the Society for Immunotherapy of Cancer (SITC) convened a task force of experts from various disciplines including, immunology, oncology, biophysics, structural biology, molecular and cellular biology, genetics, and bioinformatics to address the complexity of CIR from a holistic view. The task force was launched by a workshop held in San Francisco on May 14–15, 2018 aimed at two preeminent goals: 1) to identify the fundamental questions related to CIR and 2) to create an interactive community of experts that could guide scientific and research priorities by forming a logical progression supported by multiple perspectives to uncover mechanisms of CIR. This workshop was a first step toward a second meeting where the focus would be to address the actionability of some of the questions identified by working groups. In this event, five working groups aimed at defining a path to test hypotheses according to their relevance to human cancer and identifying experimental models closest to human biology, which include: 1) Germline-Genetic, 2) Somatic-Genetic and 3) Genomic-Transcriptional contributions to CIR, 4) Determinant(s) of Immunogenic Cell Death that modulate CIR, and 5) Experimental Models that best represent CIR and its conversion to an immune responsive state. This manuscript summarizes the contributions from each group and should be considered as a first milestone in the path toward a more contemporary understanding of CIR. We appreciate that this effort is far from comprehensive and that other relevant aspects related to CIR such as the microbiome, the individual’s recombined T cell and B cell receptors, and the metabolic status of cancer and immune cells were not fully included. These and other important factors will be included in future activities of the taskforce. The taskforce will focus on prioritization and specific actionable approach to answer the identified questions and implementing the collaborations in the follow-up workshop, which will be held in Houston on September 4–5, 2019.

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Section: Germline Genetic Contributions To Cirmentioning

confidence: 99%

“…Direct genome-editing techniques, e.g. CRISPR/Cas9 and in vivo model for studying CIR, will offer the opportunity to translate association-study based information into biological relevant knowledge [93].…”

Section: Germline Genetic Contributions To Cirmentioning

confidence: 99%